1. Field of the Invention
The present invention relates to an apparatus for biochemical testing and screening and for the performance of biochemical reactions in general. In particular, this invention relates to a dual purpose multicell device, suitable for both (a) drawing a fluid containing biochemical species through a microporous membrane, and (b) supporting a static fluid above such a membrane for an indefinite length of time.
2. Description of the Prior Art
Microtiter wells are used in biochemical laboratories for a multitude of functions, including recombinant DNA screening, hybridoma screening, and immunoassays such as the radioimmunoassay (RIA), enzyme linked immunosorbent assays (ELISA), enzymoimmuno assays (EIA), and enzyme multiplied immunoassay techniques (EMIT).
One of the known designs in current use is a multi-well plate assembly containing a binding or support matrix in the form of a planar membrane forming the bottom surface of each well. This is useful for a variety of biochemical procedures, including identification, isolation, concentration and purification of various types of species. One example is the flow-through contact between a first reactant mobile in the fluid phase and a second reactant immobilized on the support matrix. Another example is the combination of two or more reactants in the liquid phase to form a complex during prolonged retention of the fluid above the membrane, followed by drawing of the fluid and uncomplexed reactants down through the membrane to filter out the larger complex. A further example is the prolonged incubation of antibody-secreting cells or the like, followed by drawing of the surrounding fluid containing the antibodies or other selected products down through the membrane. Further procedures or combinations of the above to which this design is suitable are well known to those skilled in the art. In generalized terms, this type of assembly in order to accommodate the full range of these procedures must be capable of both retaining a fluid in the well above the membrane without substantial leakage downward beyond permeating the membrane itself, and drawing a fluid down through the membrane when desired as by negative pressure.
One example of this known design is a multiwell test plate comprised of a combination of parallel plates with holes extending therethrough according to the standard microtiter well spacing, and a flexible membrane clamped between the plates in a sandwich-type configuration. The wells are thus defined by the holes in the uppermost plate, the upper membrane surface forming the bottom of each well.
The structures currently known are characterized by uneven and unreliable sealability between the wells, poor uniformity of contact area on the membrane from one well to the next, and a lack of versatility in being able to perform both functions mentioned above. The lateral leakage and lack of uniform contact areas is a particularly serious failing since it obscures the test results when instrumentation such as a scanning densitometer is used for quantitation, by providing false or distorted readings and a high level of background counts. Even without the use of a scanning densitometer, absolute errors are often introduced by irregularities in the accessible membrane area from one well to the next. For example, in assays where one binding species is covalently bound to the membrane and the other is mobile, variations in the accessible membrane area will cause unwanted variations in the amount of the species covalently bound.